Control of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells
Control of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells
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树突状细胞中 Lkb1 对 Treg 细胞稳态和免疫平衡的控制
DOI：
10.1038/s41467-018-07545-8
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发表时间：
2018-12-13
影响因子：
16.6
通讯作者：
Feng, Xiaoming
中科院分区：
文献类型：
--
作者：
Chen, Song;Fang, Lijun;Feng, Xiaoming
为了平衡免疫和耐受性，Foxp 3+调节性T（Treg）细胞的内源性池被严格控制，但这种控制的潜在机制仍然知之甚少。在这里，我们表明，Treg细胞的数量是负调控的激酶Lkb 1在树突状细胞（DC）。条件性敲除DC中的Lkb 1基因导致多个器官中的Treg细胞过度扩增并抑制抗原特异性T细胞免疫。与野生型DC相比，Lkb 1缺陷型DC能够通过涉及NF-κB/OX 40 L通路的IKK/IKBα非依赖性激活的细胞-细胞接触增强Treg细胞增殖。有趣的是，用脂多糖治疗野生型小鼠选择性地消耗DC中的Lkb 1蛋白，导致Treg细胞扩增并抑制随后的攻击后的炎性损伤。Lkb 1的缺失并不明显上调DC上促炎分子的表达。因此，我们确定Lkb 1作为DC中的调节开关，用于控制Treg细胞稳态、免疫应答和耐受。
To balance immunity and tolerance, the endogenous pool of Foxp3+ regulatory T (Treg) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of Treg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive Treg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, Treg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in Treg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling Treg cell homeostasis, immune response and tolerance.